Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, UK.
Curr Biol. 2010 Oct 12;20(19):1752-7. doi: 10.1016/j.cub.2010.08.035. Epub 2010 Sep 16.
Many systems regulating cell polarity involve stable landmarks defined by internal cues. In the rod-shaped fission yeast Schizosaccharomyces pombe, microtubules regulate polarized vegetative growth via a landmark involving the protein Tea1. Tea1 is delivered to cell tips as packets of molecules associated with growing microtubule ends and anchored at the plasma membrane via a mechanism involving interaction with the membrane protein Mod5. Tea1 and Mod5 are highly concentrated in clusters at cell tips in a mutually dependent manner, but how the Tea1-Mod5 interaction contributes mechanistically to generating a stable landmark is not understood. Here, we use live-cell imaging, FRAP, and computational modeling to dissect dynamics of the Tea1-Mod5 interaction. Surprisingly, we find that Tea1 and Mod5 exhibit distinctly different turnover rates at cell tips. Our data and modeling suggest that rather than acting simply as a Tea1 receptor or as a molecular "glue" to retain Tea1, Mod5 functions catalytically to stimulate incorporation of Tea1 into a stable tip-associated cluster network. The model also suggests an emergent self-focusing property of the Tea1-Mod5 cluster network, which can increase the fidelity of polarized growth.
许多调节细胞极性的系统都涉及由内部线索定义的稳定地标。在杆状裂殖酵母 Schizosaccharomyces pombe 中,微管通过一个涉及蛋白质 Tea1 的地标来调节极性的营养生长。茶 1 作为与生长中的微管末端相关的分子的包被递送到细胞尖端,并通过一种涉及与膜蛋白 Mod5 相互作用的机制锚定在质膜上。茶 1 和 Mod5 以相互依赖的方式在细胞尖端的簇中高度浓缩,但 Tea1-Mod5 相互作用如何在机制上有助于产生稳定的地标尚不清楚。在这里,我们使用活细胞成像、FRAP 和计算建模来剖析 Tea1-Mod5 相互作用的动力学。令人惊讶的是,我们发现茶 1 和 Mod5 在细胞尖端表现出明显不同的周转率。我们的数据和模型表明,Mod5 不是简单地作为茶 1 的受体或作为分子“胶”来保留茶 1,而是作为一种催化因子,刺激茶 1 掺入稳定的尖端相关簇网络。该模型还表明,茶 1-Mod5 簇网络具有一种新兴的自我聚焦特性,可以提高极化生长的保真度。